ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01976.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

This review summarizes and comments on the current understanding of both the biochemical and clinical implications of the epimerization of R‐aryl propionic (APA) class (1) nonsteroidal anti‐inflammatory agents (NSAIDs) to S‐enantiomers in humans. This article focuses principally on rac‐ibuprofen and its enantiomers. In the United States, five commercialized NSAIDs are APAs. Only two of them, rac‐ibuprofen and rac‐fenoprofen, are subject to significant epimerization in humans. The remaining three, rac‐flurbiprofen, rac‐ketoprofen, and S‐naproxen, are not of interes

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01977.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Tenfold errors in pediatric doses are not uncommon. Because the needed volume of stock solution is generally small, even a tenfold higher volume may still appear deceivingly normal. Such errors are much less likely to occur in adults, because it would result in unacceptably large volumes of stock solution. Other sources of tenfold errors are communication difficulties with parents and illegible writing of orders by physicians. Testing health professionals may identify subgroups of individuals who are prone to commit such errors. Independent double checking of calculations and a mechanism to resolve disagreement is being practiced in most academic institutions. Transition to patient's unit dose is likely to decrease calculation errors, because pharmacists commit fewer errors. Hazardous drugs that are not required on a stat basis should be removed from the wards.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01978.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Simulations of time courses of drug concentrations after oral administration are frequently hampered by the lack of pharmacokinetic parameters after oral dosing. This article presents methods by which to estimate such parameters from pharmacokinetic parameters after intravenous dosing and knowledge of time of peak concentration and bioavailability after oral dosing. The application of these approaches enables the generation of meaningful graphic simulations of time courses of drug concentrations after oral administration that can have educational and illustrative uses.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01979.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single‐dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The Cmaxwere 6.4, 15.7 ± 12.0, 34.7 ± 4.6, 63.2 ± 4.6, 142.7 ± 5.6, and 131.6 ± 36.0 (means ± SD) μg/mL, respectively, and the Cmaxand AUC increased linearly with the dose. Plasma concentration‐time curves were well described by a two‐compartment open model. The plasma elimination half life of the drug was 1.88 ± 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 ± 5.1% of the dose. In the multiple‐dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The Cmaxafter the first and ninth doses were 134.0 ± 17.4 and 135.5 ± 15.5 μg/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 ± 0.8 and 1.9 ± 0.4 μg/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between the single‐ and multiple‐dose regimens. The ratio of the concentrations of the diastereomers of A and B forms measured in the plasma or urine at each point of measurement was equal to that of the standard sample, and no difference was observed in the pharmacokinetics of E1077 between the two diastereomers. The fraction of the drug bound to plasma protein was independent of the total plasma concentration and was calculated as 14.5 ± 2.9%. There were no subjective or objective abnormal findings definitely related to the drug, except that two subjects reported mild feelings of s

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01980.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48‐hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500‐mg oral dose. The dose‐adjusted maximum serum concentration (898 ± 121 ng/mL vs. 237 ± 69 ng/mL) and area under the serum concentration—time curve (9362 ± 2873 ng * hr/mL vs. 4977 ± 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 ± 0.6 hr vs. 8.4 ± 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacter

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01981.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of single, 1‐ or 2‐g intravenous doses of cefodizime were studied in subjects with normal, impaired renal function or requiring chronic hemodialysis. Drug concentrations were measured using high‐performance liquid chromatography. Forty‐five subjects (20 with creatinine clearance of ≥90 mL/min, 15 with creatine clearances between 5 and 89 mL/min, and 10 requiring chronic hemodialysis) were studied. The concentration—time curve of cefodizime was best represented by an open two‐compartment model. The elimination half‐lives in subjects with normal (Group 1) and impaired renal function (Group 2) or requiring chronic hemodialysis (Group 3) were 4.14 ± 1.55, 5.10 ± 2.24, and 10.1 ± 6.01 hours, respectively (Group 3 versus 1 or 2, P.05). The total body (serum) clearances in the same groups were 3 ± 0.52, 2.22 ± 0.61, and 0.99 ± 0.33 L/hour, respectively (Group 1 versus 2 or 3, P<.05; Group 2 versus 3, P<.05). Although renal function has an effect on the pharmacokinetics of cefodizime, its effect on the elimination half life is marginal in subjects with creatinine clearance of more than 25 mL/min. In individuals with more severe renal impairment or those requiring chronic hemodialysis, dosage adjustm

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01982.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double‐blind crossover study. Each dose administration was separated by a 1‐week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono‐conjugated) sparfloxacin levels by high‐performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 ± 158 to 1966 ± 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half‐life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by incr

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01983.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Although concentrated infusions of potassium chloride commonly are used to treat hypokalemia in intensive care unit patients, few studies have examined their effects on plasma potassium levels. Forty patients with hypokalemia were given infusions of 20 mmol of potassium chloride in 100 mL of normal saline over 1 hour; 26 patients received the infusions through the central vein and 14 patients through the peripheral vein. Plasma potassium ([K]p) was measured at 15‐minute intervals during and after the infusion in 31 patients. ΔK was defined as the difference between each potassium determination and baseline plasma potassium concentration. Continuous electrocardiographic recording was carried out during the infusion and during the 1‐hour period immediately preceding the infusion. Mean baseline [K]pwas 2.9 mmol/L and all subsequent plasma concentrations significantly increased from baseline. Mean peak [K]pwas 3.5 mmol/L, [K]p(1 hour postinfusion) was 3.2 mmol/L, and mean postinfusion ΔK was 0.48 mmol/L (range −0.1–1.7 mmol/L). Arrhythmias, changes in cardiac conduction intervals, and other complications did not occur. The frequency of premature ventricular beats decreased significantly during the infusion compared with that of the control period. The high concentration (200 mmol/L) and rate of delivery (20 mmol/hr) of the potassium chloride infusions were well tolerated, decreased the frequency of ventricular arrhythmias, and did not cause transient hyp

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01984.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The safety and efficacy of intravenous (IV) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with IV torsemide and six patients, with IV furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were administered initially. The dose was titrated as necessary over the next 24 hours. In patients who received IV torsemide, median fractional sodium excretion significantly increased from 2.88% (0.04–10.1%) at baseline to 6.76% (0.71–11.6%) at peak (P =0.0342). Hourly urine volume increased from 134 mL (25–400 mL) to 375 mL (145–790 mL) (P =0.0034). Torsemide administration resulted in a significant improvement in both pulmonary rales and orthopnea. None of the patients experienced serious adverse events or required withdrawal from the study. These results suggest that IV torsemide is an effective and well‐tolerated diuretic in patients with acute cardiogenic pulmon

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb01985.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY